Impact of elexacaftor/tezacaftor/ivacaftor on lung function, nutritional status, pulmonary exacerbation frequency and sweat chloride in people with cystic fibrosis: real-world evidence from the German CF Registry
Authors: Sivagurunathan Sutharsan, Stefanie Dillenhoefer, Matthias Welsner, Florian Stehling, Folke Brinkmann, Manuel Burkhart, Helmut Ellemunter, Anna-Maria Dittrich, Christina Smaczny, Olaf Eickmeier, Matthias Kappler, Carsten Schwarz, Sarah Sieber, Susanne Naehrig, Lutz Naehrlich, Klaus Tenbrock, Claus Pfannenstiel, Dirk Steffen, Jochen Meister, Britta Welzenbach, Anette Scharschinger, Markus Kratz, Maike Pincus, Tobias Tenenbaum, Mirjam Stahl, Kerstin Landwehr, Stefanie Dillenhöfer, Hans Kössel, Petra Kaiser, Manfred Käding, Simone Stolz, Stefan Blaas, Jutta Hammermann, Monika Gappa, Antje Schuster, Dana Spittel, Sabine Zirlik, Sabina Schmitt, Florian Stehling, Sivagurunathan Sutharsan, Joachim Bargon, Malte Cremer, Christina Smaczny, Sebastian Fähndrich, Andrea Heinzmann, Lutz Nährlich, Stefan Kuhnert, Sebastian Schmidt, Bettina Wollschläger, Anna Nolde, Inka Held, Wolfgang Kamin, Felix C. Ringshausen, Anna-Maria Dittrich, Sabine Wege, Olaf Sommerburg, Norbert Geier, Sara Lisa Fleser, Heinrike Wilkens, Helmut Ellemunter, Michael Lorenz, Paul Vöhringer, Martin Schebek, Christian Timke, Ingrid Bobis, Thomas Nüßlein, Doris Dieninghoff, Ernst Rietschel, Bastian Klinkhammer, Freerk Prenzel, Alexandra Wald, Axel Kempa, Folke Brinkmann, Eva Lücke, Ines Adams, Krystyna Poplawska, Simone Lehmkühler, Monika Bauck, Anne Pfülb, Rainald Fischer, Gudrun Schopper, Susanne Nährig, Matthias Griese, Jörg Grosse, Peter Küster, Birte KinderHolger Köster, Susanne Büsing, Margarethe Pohl, Carsten Schwarz, Andreas Artlich, Alexander Kiefer, Manfred Ballmann, Nikola Gjorgjevski, Markus A. Rose, Friederike Ruf, Rolf Mahlberg, Wolfgang Thomas, Ute Graepler, Sebastian Bode, None hilipp Meyn, Josef Rosenecker, Cordula Koerner, Klaus-Michael Keller, Tina Teßmer, Helge Hebestreit, Gerhild Lohse
Journal: The Lancet Regional Health - Europe (2023)

Treatment with elexacaftor/tezacaftor/ivacaftor (ETI) improves multiple clinical outcomes in people with cystic fibrosis (pwCF) with at least one F508del allele. This study evaluated the real-world impact of ETI on lung function, nutritional status, pulmonary exacerbation frequency, and sweat chloride concentrations in a large group of pwCF.This observational cohort study used data from the German CF Registry for pwCF who received ETI therapy and were followed up for a period of 12 months.The study included 2645 pwCF from 67 centres in Germany (mean age 28.0 ± 11.5 years). Over the first year after ETI was initiated, percent predicted forced expiratory volume in 1 s (ppFEV1) increased by 11.3% (95% confidence interval [CI] 10.8-11.8, p < 0.0001), body mass index (BMI) z-score increased by 0.3 (95% CI 0.3-0.4, p < 0.0001) in individuals aged 12 to <18 years and BMI in adults increased by 1.4 kg/m2 (95% CI 1.3-1.4, p < 0.0001), pulmonary exacerbations decreased by 75.9% (p < 0.0001) and mean sweat chloride concentration decreased by 50.9 mmol/L (95% CI -52.6, -49.3, p < 0.0001). Improvements in ppFEV1 over the first year of therapy were greater in pwCF who had not previously received cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy (12.6% [95% CI 11.9-13.4] vs. 9.7% [95% CI 9.0-10.5] in those with prior CFTR modulator treatment.These real-world data are consistent with the findings of randomised clinical trials, and support the use of ETI as a highly effective treatment option for pwCF who have at least one F508del allele.None.